LABORATORY OF NEUROBIOLOGY (LNb)

1. Scientific directions of the laboratory

• • To study the role of the nervous system in ethiopathogenesis of the peripheral diseases (tumors, metabolic). We are focusing on investigation of the mechanisms and neuronal pathways involved in the signaling related to the pathological processes in the peripheral tissues, processing of the signals in the brain and on the adaptive/compensatory responses of central nervous system to the pathological processes at the periphery.
• • To study the role of signals transmitted by afferent neuronal pathways to the brain on the neuroendocrine stress response of the organism: role of the vagus nerve in the regulation of sympathoadrenal activity during the stress reaction, role of the feedback mechanism of the vagus nerve afferent pathways on the activity of catecholaminergic neurons and adrenal medulla in the rat.
• • To study the potential of therapeutic application of stem cells in treatment of experimental glioblastoma.

2. Selected results and their acceptance

We introduced concept of neurobiology of the cancer disease to the scientific literature. Apart from theoretic works, we have shown that signals from the tumors are transmitted and processed in the brain, particularly in brainstem and hypothalamus, areas known for their involvement in the immune reaction of the organism. We also described the dynamics of changes in individual brain areas activity during the tumor growth. These results contributed to better understanding of the role of the central nervous system in etiopathogenesis of cancer disease.

We have shown that interruption of vagal pathways leads to increased activity of the sympathoadrenal system during stress response of the organism. This observation suggests that the vagus nerve plays an important role in the neuro-endocrine stress response of the organism. Inhibitory function of the vagus nerve can ameliorate harmful effect of excessive release of catecholamines on the peripheral tissues.

3. Current projects and collaborations:

• Neurobiology of tumors: study the role of the nervous system in ethiopatogenesis of tumor growth and metastasis formation (APVV-0007-10): This project is the continuation of the previous APVV grant and is focused on characterization of changes in activity of selected brain areas in the rat with tumors, on characterization of functional innervations of tumor tissue by using retrograde marker dyes and on monitoring of the effects of intervention in central and peripheral nervous system on tumor growth.
• The role of the vagus nerve in regulation of sympathoadrenal system in rat under basal and stressful situations (VEGA 2/0010/09): In this project we have studied the effect of interruption of signal transmitted by afferent pathways of the vagus nerve on the stress reaction by measuring plasmatic levels of catecholamines and corticosterone. In current stage of our research we are studying the effect signal transmission from peripheral tissues on the extent of neuro-endocrine stress response with the focus on the heart.
• Investigation of potential therapeutic use of stem cells in the treatment of glioblastoma: Cooperation on the project of Professor Čestmír Altaner, DSc. from the Institute of Experimenta Oncology SAS.

International cooperation:

Yori Gidron, PhD (Professor of Behavior Medicine, Faculty of Medicine & Pharmacy 103, Laarbeeklaan, Jette, 1090 Free University of Brussels (VUB), Belgium): “Investigation of the role of the nervous system in the regulation of the tumor growth”

Luca Vannucci, MD, PhD. (Laboratory of Natural Cell Imunity, Department of Immunology and Gnotobiology, Institute of Microbiology Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 4, 142 20, Czech Republic: “Investigation of the effect of the electric stimulation of the vagus nerve on the tumor growth”

Lisa E. Goehler, PhD. (Associate Professor of Nursing Research Neuroimmunology & Behavior Center for the Study of Complementary & Alternative Therapies School of Nursing, P.O. Box 800782 University of Virginia, Charlottesville, VA 22908: “Investigation of the activity of neurons in different brain areas in tumors bearing rats”

4. Methodological approaches and techniques used in our laboratory:

• induction of experimental tumors: BP6 fibrosarcoma, Yoshida ascites hepatoma
• stereotactic interventions in the brain: acute and chronic application of drugs and cells, surgical lesions of brain areas and pathways
• cannulation techniques: cannulation of jugular vein, tail artery
• biochemical and molecular biology techniques: ELISA, RealTime PCR
• tail-cuff method for the blood pressure measurement in the rats
• telemetric measurement of the heart rate, blood pressure and body temperature in the rats
• electrophysiological methods: stimulation of peripheral nerves

5. List of the most significant publications of the members of the Laboratory of Neurobiology (IF ≥2).

1. Ondicova K, Mravec B. Role of nervous system in cancer aetiopathogenesis. Lancet Oncol 2010; 11: 596–601. IF 14, 470

2. Mravec B, Gidron Y, Hulin I.: Neurobiology of cancer: interactions between nervous, endocrine and immune systems as a base for monitoring and modulating the tumorigenesis by the brain. Semin Cancer Biol 2008; 18: 150-63. IF 7, 758

3. Altanerova V, Cihova M, Babic M, Rychly B, Ondicova K, Mravec B, Altaner C. Human adipose tissue–derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat glioblastoma. Int J Cancer 2012; 130: 2455-63. IF 4,92

4. De Couck M, Mravec B, Gidron Y. You may need the vagus nerve to understand pathophysiology and to treat diseases. Clin Sci 2012; 122: 323-8. IF 4,613

5. Mravec B. The brain as a target for development of new class of drugs for the treatment of somatic diseases. Exp Opion Ther Targ 2012; 16: 433-7. IF 3,649

6. Nostramo R, Tillinger A, Saavedra JM, Kumar A, Pandey V, Serova L, Kvetnansky R, Sabban EL. Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress. J Endocrinol 2012; 215: 291-301. IF 3,548

7. Mravec B, Gidron Y, Kukanova B, Bizik J, Kiss A, Hulin I. Neural – endocrine – immune complex in the central modulation of tumorigenesis: facts, assumptions, and hypotheses. J Neuroimmunol 2006; 180: 104-16. IF 2,901

8. Tillinger A, Novakova M, Pavlovicova M, Lacinova L, Zatovicova M, Pastorekova S, Krizanova O, Kvetnansky R. Modulation by 6-hydroxydopamine of expression of the phenylethanolamine N-methyltransferase (PNMT) gene in the rat heart during immobilization stress. Stress 2006; 9: 207-13. IF 2,553

9. Pirnik Z, Bundzikova J, Francisty T, Cibulova E, Lackovicova L, Mravec B, Kiss A. Effect of liver ischemia-reperfusion injury on the activity of neurons in the rat brain. Cell Mol Neurobiol 2009; 29: 951-60. IF 2,107

10. Pirnik Z, Bundzikova J, Bizik J, Hulin I, Kiss A, Mravec B. Activity of brainstem groups of catecholaminergic cells in tumor bearing rats: response to immobilization stress. Ann NY Acad Sci 2008; 1148: 141-7. IF 2,101